Integrated high-strength implant and manufacturing method

Abstract

The invention belongs to the field of dental implant, and particularly relates to an integrated high-strength implant and a manufacturing method.The high-strength implant comprises an implant body and an abutment, the abutment is arranged at the end of the implant body, the abutment and the implant body are integrally formed, uniform first-level and second-level holes are formed in the surface of the implant body, the diameter of the first-level hole is 20-100 micrometers, and the diameter of the second-level hole is 20-100 micrometers. And the diameter of the secondary holes is 1-10 [mu] m. The implant provided by the invention has excellent mechanical properties and biocompatibility.

Description

Technical Field

[0001] The present invention belongs to the field of dental implants, and particularly relates to an integrated high-strength implant and a manufacturing method thereof. Background Art

[0002] An implant is an artificial tooth used to replace natural teeth to perform chewing, pronunciation, and aesthetic functions after tooth defect or loss. Commonly used materials are pure titanium or titanium alloys, which have good bone integration performance. However, metal materials have defects such as ion dissolution, allergy, gray line at the cervical margin, translucency, and easy adhesion of bacteria, making the research and development of alternative materials imperative.

[0003] Due to their good biocompatibility and aesthetics, ceramic materials have gradually become a new generation of artificial tooth implant materials. In the past decade or more, ceramic implants have been successively applied clinically. However, during the use of ceramic implants, there are also phenomena such as fracture, infection, and insufficient bone bonding.

[0004] The reasons for the above phenomena mainly include the following three aspects: 1) The external shape structure design of the ceramic implant has defects, resulting in stress concentration in a smaller area. This area is under excessive force for a long time, leading to fracture; 2) Defects in the manufacturing process of the ceramic implant (including forming, sintering, machining, etc.) result in difficulties in meeting requirements such as densification and strength of the ceramic implant; 3) The surface treatment of the ceramic implant is difficult. Since ceramic materials usually have high hardness and high surface treatment difficulty, the surface structure, morphology, and roughness formed by the surface treatment process are not ideal, resulting in fewer bone bonding sites and insufficient bone bonding amount. Summary of the Invention

[0005] In order to improve the deficiencies of the prior art, the present invention provides an integrated high-strength implant and a manufacturing method thereof. The implant obtained by this method has excellent mechanical properties and biocompatibility.

[0006] In a first aspect, the present invention provides an integrated high-strength implant, including an implant body and a abutment. The abutment is provided at the end of the implant body, and the abutment and the implant body are integrally formed. The surface of the implant body has uniform primary and secondary holes. The diameter of the primary holes is 20 - 100 μm, and the diameter of the secondary holes is 1 - 10 μm.

[0007] According to an embodiment of the present invention, the abutment is used to extend outside the gingiva to form a part passing through the gingiva and inside the oral cavity and connect with a prosthesis. The implant body and the abutment are manufactured by an integrated forming technique, avoiding the connection problems in the traditional two-piece design and improving the stability and durability of the overall structure.

[0008] According to an embodiment of the present invention, a square groove is provided inside the abutment, and the square groove is used to connect the dental crown. The square groove makes the dental crown more resistant to rotation, improving the accuracy and convenience of wearing the tooth.

[0009] According to an embodiment of the present invention, a connecting groove is provided on the outer wall of the abutment, and the connecting groove is used to cooperate with an external carrier and a protective cap. For example, the external carrier can be snapped into the groove. When in use, when the user transfers or uses the implant by clamping the carrier, the number of times of touching the implant can be reduced, avoiding contamination and scratching of the implant surface. At the same time, it is easy to pick up and place the implant.

[0010] According to an embodiment of the present invention, the implant includes a soft tissue connection area and a threaded area. The soft tissue connection area is located at the upper part of the implant. When the implant is implanted, the soft tissue connection area corresponds to the soft tissue. The soft tissue connection area has an arc-shaped structure. The soft tissue connection area can provide an attachment platform for the soft tissue, forming a hemidesmosome connection, preventing bacteria from entering the alveolar bone and causing inflammation, resulting in implant failure.

[0011] According to an embodiment of the present invention, a cutting edge is provided at the lower part of the threaded area, and the cutting edge is eccentric by 0.1 - 0.5 mm. Preferably, the cutting edge is eccentric by 0.1 - 0.3 mm.

[0012] According to an embodiment of the present invention, the threaded area includes a matrix, and the threads protrude radially outward from the surface of the matrix. The diameter of the threaded area gradually decreases from top to bottom, and the bottom diameter of the threaded area is 0.1 - 0.5 mm smaller than the top diameter.

[0013] According to an embodiment of the present invention, the threads in the threaded area are multi-start threads, such as double-start or triple-start threads. The lead of the multi-start thread (i.e., the distance the thread advances axially per revolution) is a multiple of the single-start thread with the same pitch. This greatly reduces the time of the implantation surgery. For example, the lead of the triple-start thread is three times the pitch of the single-start thread, thus accelerating the implantation speed.

[0014] According to an embodiment of the present invention, the surface of the thread is a smooth structure.

[0015] In a second aspect, the present invention provides a method for forming the above-mentioned integrated high-strength implant, including the following steps:

[0016] S1. Loading ceramic powder into a mold, sealing it, and performing cold isostatic pressing to obtain a green body;

[0017] S2. Debinding and sintering the green body to obtain a blank;

[0018] S3. Machining the blank to obtain a semi-finished implant;

[0019] S4. Performing sandblasting and acid etching on the semi-finished implant to obtain the implant.

[0020] According to an embodiment of the present invention, the ceramic powder is at least one of alumina powder, zirconia powder, alumina toughened zirconia powder or zirconia toughened alumina powder, for example, zirconia powder.

[0021] According to an embodiment of the present invention, the particle size of the zirconia powder is 1 to 100 nm, preferably the particle size of the zirconia powder is 5 - 50 nm, and further preferably, the particle size of the zirconia powder is 10 - 30 nm.

[0022] According to an embodiment of the present invention, the mold is made of an elastic material, and the elastic material is, for example, rubber or plastic.

[0023] According to an embodiment of the present invention, the cold isostatic pressing includes the following steps: placing the mold filled with ceramic powder into the high-pressure cavity of a cold isostatic press, starting the machine, gradually applying pressure to 250 ± 50 MPa, maintaining the pressure for 5 - 10 minutes, and compacting the powder under uniform pressure.

[0024] According to an embodiment of the present invention, between step S1 and S2, the following steps are included: depressurizing the high-pressure cavity at a rate of 15 ± 5 MPa / min, demolding to obtain a green body.

[0025] According to an embodiment of the present invention, the debinding includes the following steps: keeping the green body at a temperature of 400°C - 700°C for 2 - 4 hours.

[0026] According to an embodiment of the present invention, the sintering includes the following steps: first debinding the green body, and then keeping it at 1200°C - 1650°C for 2 - 6 hours.

[0027] According to an embodiment of the present invention, the debinding includes the following steps: heating the green body at a rate of 50 - 100°C / h to 700°C - 1200°C, keeping it for 1 - 2 hours, and then heating it at a rate of 100 - 200°C / h to the sintering temperature.

[0028] According to an embodiment of the present invention, between step S2 and S3, the following steps are included: cooling the sintered green body at a rate of 100°C ± 20°C / h to below 450°C ± 100°C, and then naturally cooling it to room temperature to obtain an implant blank.

[0029] According to an embodiment of the present invention, the machining includes rough machining and finish machining. Among them, for rough machining, a common alloy end mill is used, and the tool is selected with a diameter of 5 - 10 mm. For finish machining, a special alloy end mill with a selected diameter of 1 - 10 mm is used.

[0030] According to an embodiment of the present invention, first, the machined implant semi-finished product is subjected to sandblasting treatment.

[0031] According to an embodiment of the present invention, the sandblasting treatment includes spraying sand balls onto the surface of the semi-finished implant. Preferably, the sand balls are selected from boron carbide, zirconia or alumina, preferably zirconia, and more preferably alumina. Preferably, the diameter of the sand balls is 50 - 500 μm, preferably 80 - 400 μm, and more preferably 100 - 200 μm. Further, the pressure of the sandblasting is 1 - 10 bar, for example 2 - 5 bar; the working distance of the sandblasting is 10 - 50 mm, for example 15 mm, preferably 8 - 10 mm; the moving speed of the sandblasting is 1 - 20 mm / s, for example 5 mm / s.

[0032] According to an embodiment of the present invention, the etching treatment includes: etching the surface of the sandblasted semi-finished implant with an etching solution.

[0033] According to an embodiment of the present invention, the etching solution includes a first acid and hydrofluoric acid. Preferably, the first acid can be selected from at least one, two or more of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, etc. Further, the hydrofluoric acid is selected from 30 - 50 vol% hydrofluoric acid; the first acid is selected from 50 - 80 vol% nitric acid or 30 - 50 vol% sulfuric acid, 40 - 60 vol% phosphoric acid. More preferably, the etching solution is obtained by mixing 30 - 50 vol% hydrofluoric acid and 50 - 80 vol% nitric acid, preferably by mixing 35 - 45 vol% hydrofluoric acid and 60 - 70 vol% nitric acid. Exemplarily, the etching solution includes hydrofluoric acid (40 vol%) and nitric acid (50 vol%), and the volume ratio of the two is 4:6.

[0034] According to an embodiment of the present invention, in the etching solution, the volume ratio of the hydrofluoric acid to the first acid is (2 - 8):(8 - 2), preferably (4 - 6):(6 - 4), and more preferably 4:6.

[0035] According to an embodiment of the present invention, the etching time is 1 min - 120 min, preferably 20 - 40 min, and more preferably 30 min.

[0036] According to an embodiment of the present invention, the etching temperature is 30 - 100 °C, for example 70 °C, 80 °C.

[0037] Beneficial effects

[0038] 1) The integrated high-strength implant in the present invention includes an implant and a abutment. The abutment is arranged at the end of the implant, and the abutment and the implant are integrally formed. The integrated implant is easy to install, improving the surgical efficiency; at the same time, it avoids the connection problems in the traditional two-stage design, improving the stability and durability of the overall structure.

[0039] 2) In the integrated high-strength implant of the present invention, a threaded area is provided at the lower part of the implant. The diameter of the threaded area gradually decreases from top to bottom, and the threads in the threaded area are multi-start threads. The multi-start threads not only have a larger lead but also a larger surface area, which can accelerate the implantation speed, provide more attachment sites, and improve the stability of the implant.

[0040] 4) In the integrated high-strength implant of the present invention, the threads in the threaded area are smooth threads, which can avoid stress concentration, achieve the effect of dispersing force, reduce the occurrence of mechanical complications of the implant, and improve the success rate of the surgery.

[0041] 5) The material in the present invention is zirconia ceramic material. Zirconia powder with a particle size of 5 - 50 nanometers is selected and formed under specific conditions such as temperature and pressure. The content of monoclinic phase before aging of the obtained zirconia implant embryo is less than 2%, and the content of monoclinic phase after aging is less than 3%; the four-point bending strength before aging is greater than 2000 MPa, the four-point bending strength after aging is greater than 1800 MPa, the fracture toughness is greater than 10 MPa·m 1 / 2 , the Young's modulus is greater than 210 GPa, and the hardness is greater than 12 GPa. Therefore, the implant has high strength and a long service life; and zirconia ceramic has good light transmittance and color stability, which can meet the aesthetic requirements of patients.

[0042] 6) The inventor unexpectedly found that by first performing sandblasting and then acid etching treatment under specific conditions, uniform primary and secondary pores are formed on the surface of the implant. The diameter of the primary pores is 20 - 100 μm, and the diameter of the secondary pores is 1 - 10 μm. The formed primary and secondary pores enable osteoblasts to grow in the cavities, greatly improving the stability of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 is a schematic structural diagram of the integrated high-strength implant in cooperation with the carrier ( Figure 1 in which, the schematic view in the A direction refers to the top view and the bottom view along the A direction);

[0044] Figure 2 is a physical diagram of the integrated high-strength implant;

[0045] Figure 3 is a schematic diagram for measuring the surface area of the product of the single-start thread part;

[0046] Figure 4 is a schematic diagram for measuring the surface area of the product of the double-start thread part;

[0047] Figure 5 is a schematic diagram of the static compression of the YY / T 0521-2018 product;

[0048] Figure 6Schematic diagram of the finite element analysis result of the non-smooth design at the thread

[0049] Figure 7 Schematic diagram of the finite element analysis result of the smooth design at the thread

[0050] Figure 8 Process flow chart for manufacturing ceramic dental implants

[0051] Figure 9 ×100 view under electron microscope after sandblasting and acid etching of ceramic implants

[0052] Figure 10 ×500 view under electron microscope after sandblasting and acid etching of ceramic implants

[0053] Figure 11 ×2000 view under electron microscope after sandblasting and acid etching of ceramic implants

[0054] Figure 12 ×5000 view under electron microscope after sandblasting and acid etching of ceramic implants

[0055] Figure 13 Curve graph of the body weight of experimental animals changing with the cycle in animal experiments

[0056] Figure 14 Pictures of the Micro-CT examination results of the ceramic implants in the experimental group and the control group after bone cell growth at 4 weeks, 8 weeks, 13 weeks, and 26 weeks after surgery in animal experiments

[0057] Figure 15 Curve graph of the total bone volume changing with the cycle in animal experiments

[0058] Figure 16 Pictures of methylene blue and acid fuchsin staining of hard tissue sections of the ceramic implants in the experimental group and the control group after bone cell growth at 4 weeks, 8 weeks, 13 weeks, and 26 weeks after surgery in animal experiments

[0059] Figure 17 Curve graph of the BIC(%) binding rate changing with the cycle in animal experiments

[0060] Figure 18 Analysis diagram of hard tissue sections in animal experiments

[0061] Figure 1 In it, 1 - implant, 2 - abutment, 3 - connecting groove, 4 - soft tissue connection area, 5 - thread area, 6 - cutting edge. Specific implementation manner

[0062] The following will further elaborate on the structure of the present invention in conjunction with specific embodiments. It should be understood that the following embodiments are only for illustrative explanation of the present invention and should not be construed as limiting the protection scope of the present invention. All technologies implemented based on the above content of the present invention are covered within the scope of protection intended by the present invention.

[0063] In the description of the present invention, it should be noted that the orientation or positional relationship indicated by the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings. It is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as limiting the present invention.

[0064] In the description of the present invention, it should be noted that unless otherwise clearly specified and defined, the terms "installed", "connected", and "coupled" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0065] Embodiment 1 Structure of an Integrated High-Strength Implant

[0066] See Figure 1 As shown, the integrated high-strength implant includes an implant 1 and an abutment 2. The abutment 2 is provided at the end of the implant 1, and the abutment 2 is integrally formed with the implant 1. The abutment 2 is used to extend to the outside of the gum, forming the part passing through the gum, and connecting with the prosthesis. The implant 1 and the abutment 2 are made by an integrated molding technique, avoiding the connection problems in the traditional two-stage design and improving the stability and durability of the overall structure.

[0067] A square groove is provided inside the abutment 2. The square groove is used to connect the crown. The square groove makes the crown more anti-rotation, improving the accuracy and convenience of wearing the tooth.

[0068] And a connection groove 3 is provided on the outer wall of the abutment 2. See Figure 2 As shown, the connection groove 3 is used to cooperate with an external carrier. For example, the external carrier can be snapped into the groove 3. When in use, when the user transfers or uses the implant 1 by clamping the carrier, the number of times of touching the implant 1 can be reduced, avoiding scratching the surface of the implant 1. At the same time, it is easy to pick up and place the implant.

[0069] The implant 1 includes a soft tissue connection area 4 and a threaded area 5. The soft tissue connection area 4 is located at the upper part of the implant 1. When the implant 1 is implanted, the soft tissue connection area corresponds to the soft tissue. The soft tissue connection area 4 has an arc-shaped structure, and the radian of the arc structure is R1 - R5. The soft tissue connection area 4 can provide an attachment platform for the soft tissue, and the arc-shaped structure can fit and cover the surface of the soft tissue, forming a hemidesmosome connection between the two, forming a seamless structure, preventing bacteria from entering the alveolar bone through the gap between the soft tissue connection area 4 and the soft tissue, causing inflammation, and thus leading to implant failure.

[0070] A cutting edge 6 is provided at the lower part of the threaded area 5. The height of the cutting edge 6 is 5 - 10 mm, and the cutting edge 6 is eccentric by 0.1 - 0.5 mm. The purpose of setting the cutting edge 6 is to make it easier for the operator of the implant 1 to implant the product. As is well known, M = F × L. When the torque M is constant, the smaller L is, the larger F is, and the greater the cutting force generated, so the more labor-saving it is. The bottom end of the implant 1 is circular, which can prevent the perforation of the maxillary sinus and make the product safer.

[0071] The threaded area 5 includes a substrate, and the threads protrude radially outward from the surface of the substrate. The diameter of the threaded area 5 gradually decreases from top to bottom. The bottom diameter of the threaded area 5 is 0.1 - 0.5 mm smaller than the top diameter. The larger the diameter of the threaded area 5, the greater the shear force that the implant 1 can withstand, and the larger the contact area with the alveolar bone, and the better the stability of the product. This design increases the mechanical stability of the product.

[0072] The threaded area 5 with a gradually decreasing diameter from top to bottom (hereinafter referred to as the tapered thread) has the following advantages:

[0073] I. In terms of initial stability

[0074] 1. During the implantation process of the dental implant with tapered threads, the outer diameter of the threads gradually decreases from top to bottom. This structure enables the implant to have a closer contact with the surrounding bone tissue. For example, at the initial stage of implantation, the thicker threads can first contact the bone cortex. As the implantation depth increases, the threads gradually become thinner and can better fit the cancellous bone. This close fit is like a special key inserted into the corresponding lock hole, increasing the friction between the implant and the bone tissue, thus effectively improving the initial stability of the implant.

[0075] 2. Compared with traditional equidistant and equal-thickness threads, tapered threads can adaptively fit according to different bone quality conditions (such as areas with different bone densities). They can also better grip the bone tissue in areas with lower bone density, reducing the micromotion of the implant after implantation, and creating good conditions for subsequent bone bonding.

[0076] 3. The tapered thread can better disperse the stress on the implant under functional loading to the surrounding bone tissue. When the patient chews food and generates a biting force, the implant is subjected to axial and lateral forces. The tapered thread structure can make the stress more evenly distributed to the bone tissue along the tapered direction of the thread.

[0077] II. Osseointegration

[0078] 1. The tapered thread structure is similar to building a "growth track" for osteocytes, which is conducive to the deposition and growth of new bone on the implant surface. Compared with traditional threads, the tapered thread can promote the contact and combination of bone tissue and the implant at an early stage after implantation, shortening the time of osseointegration.

[0079] 2. Increase the osseointegration area: Due to the shape characteristics of the tapered thread, it can provide a larger osseointegration area under the same implant size. As the thread tapers, the contact area between the implant surface and the bone tissue increases in three-dimensional space. For example, during the process of the thread changing from thick to thin, the contact mode between each turn of the thread and the bone tissue is different. Overall, it can enable more bone tissue to interact with the implant surface, which is like building a more extensive "connection bridge" between the implant and the bone tissue, thereby improving the quality and strength of osseointegration and facilitating the long-term stable existence of the implant in the jawbone.

[0080] III. Aesthetic effects

[0081] 1. Gingival form maintenance: The tapered thread implant has a good supporting effect on the gingival tissue. After implant restoration, the appropriate implant structure helps to maintain the natural form of the gingiva. Due to its good primary stability and osseointegration performance, the bone tissue around the implant can remain stable, thereby providing stable support for the gingiva. For example, in single-tooth implant restoration, the tapered thread implant can avoid gingival recession caused by implant loosening or bone resorption, making the contour of the gingival margin more natural and beautiful, meeting the requirements of aesthetic restoration.

[0082] 2. Reduce soft tissue complications: The tapered thread implant is beneficial to the health of the soft tissue around the implant. The tapered thread enables the implant to better adapt to the physiological environment in the oral cavity and reduces the irritation to the surrounding soft tissue because it can maintain a stable position during implantation and functional loading and will not cause damage to soft tissues such as the gingiva due to micro-movement and other situations.

[0083] 3. Compared with non-tapered thread implants, the tapered thread implant can reduce the incidence of soft tissue complications such as peri-implantitis, which is beneficial to maintaining the oral soft tissue aesthetics and health after implant restoration.

[0084] The threads in the threaded area 5 are multi-start threads, such as double-start or triple-start threads. The lead of a multi-start thread (i.e., the distance the thread advances axially per revolution) is a multiple of the pitch of a single-start thread with the same pitch. This significantly reduces the time of the implantation surgery. For example, the lead of a triple-start thread is three times the pitch of a single-start thread, thus accelerating the implantation speed.

[0085] The multi-start thread design can increase the thread density and surface area while maintaining a relatively fast implantation speed. See Figure 3 and Figure 4 shown, which are the schematic diagrams for measuring the surface area of the threaded part of a single-start thread and the threaded part of a double-start thread. Among them, the surface area of the threaded part of the single-start thread structure is 172.26 square millimeters, and the surface area of the threaded part of the double-start thread is 174.11 square millimeters. It can be seen that the surface area of the multi-start thread is larger, which can provide more attachment sites, enabling the implant 1 to obtain better stability in the initial stage. This design helps to reduce the vibration and displacement of the implant 1 after implantation, thereby improving the long-term success rate of the implant 1.

[0086] Furthermore, the threaded structure is an important structure for maintaining the bone mass in the neck area. When the implant 1 functions, the force transmitted by the implant 1 with a smooth neck design to the bone-implant interface is mainly shear force, which is the most harmful force to bone tissue. Compared with shear force, bone tissue has a higher tolerance to compression and tension. In the present invention, the design of the multi-start thread changes the type of force at the bone-implant interface, increasing the tolerance of the bone tissue around the implant, thereby effectively reducing the bone resorption at the implant neck.

[0087] The neck is of a threaded structure, enabling the implant to better adapt to the physiological functions of the surrounding bone and preserve the surrounding bone. The large threads at the lower part of the implant mainly increase the mechanical stability in the initial stage and the bone integration stability in the later stage. The threads in the neck do not play a role in increasing the initial stability in the initial stage but reduce the stress concentration in the neck. In the later stage, they reduce the stress concentration during the occlusion process, convert the shear force into tensile stress or compressive stress, reduce bone resorption, and promote bone integration.

[0088] When the material of the implant is zirconia, since the failure of the implant 1 made of zirconia is usually due to stress concentration, which causes the point of stress concentration to crack and then extend to a line, and further leads to the overall rupture of the implant 1. To solve this problem, the present invention selects arc-shaped threads, and a smooth design with R0.1 - R0.5 is achieved at the arc-shaped threads to avoid stress concentration and achieve the effect of dispersing force, greatly improving the success rate of the surgery. Among them, the thread profile angle of the arc-shaped thread is 30 - 60°, and the thread height is 0.3 - 0.6 mm.

[0089] According to the product embedding method and mechanical loading method of YY / T 0521-2018, a static pressure of 200 N was applied to the smoothed implant and the unsmoothed implant in this embodiment at the same time for analysis (the other structures of the two implants are the same, and three parallel tests were carried out for each implant), see Figure 5 As shown, it is a schematic diagram of the static compression of the YY / T 0521-2018 product.

[0090] See Figure 6 and Figure 7 As shown (wherein, the thread was calculated 3 times and the 3 averages were taken), the implants corresponding to the smoothed and unsmoothed threads were analyzed by the finite element method three times and statistically analyzed. As shown in Table 1 and Table 2, the average value of the maximum stress received by the product with an unsmoothed thread design was 851.97 Mpa, and the average value of the maximum stress received by the product with a smoothed thread design was 644.03 Mpa. It can be seen from this that the local stress of the smoothed thread design of the implant 1 is smaller than that of the unsmoothed thread design of the product, that is, the smoothed thread design of the product can effectively disperse stress and avoid stress concentration.

[0091] Table 1 Finite element analysis results of implants with unsmoothed threads

[0092]

[0093] Table 2 Finite element analysis results of implants with smoothed threads

[0094] Group Maximum Stress 1 642.7 Mpa 2 644.4 Mpa 3 645.0 Mpa Average Value 644.03 Mpa

[0095] Forming method of the integrated high-strength implant in Example 2

[0096] The raw material in this embodiment is zirconia powder. The selection of zirconia powder directly affects the mechanical properties of the manufactured implant. The inventor unexpectedly found that when the particle size of the zirconia powder is 5-50 nanometers, the mechanical properties of the manufactured implant are the best.

[0097] See Figure 8 As shown, the forming method of the zirconia powder includes the following steps:

[0098] I. Powder loading and cold isostatic pressing:

[0099] Put the zirconia powder into an elastic mold, seal it and put it into a high-pressure container. Through a high-pressure pump, a uniform static pressure is generated on the mold by the liquid medium, and the powder is compacted under isotropic pressure to form a green body with a certain density and strength.

[0100] 1) Mold preparation:

[0101] Design and fabricate an elastic mold according to the shape and size of the implant. Usually, materials such as rubber or plastic are used to ensure that the mold has good flexibility and sealing performance.

[0102] 2) Compaction:

[0103] Load an appropriate amount of zirconia powder into the mold and place it in the high-pressure chamber of a cold isostatic press. Start the machine and gradually apply pressure to about 250 ± 50 MPa, and maintain the pressure for 5 - 10 minutes to compact the powder under uniform pressure.

[0104] 3) Demolding treatment:

[0105] After pressing is completed, slowly release the pressure until the pressure is reduced to 0 MPa before removing the mold. The pressure release rate is 15 ± 5 MPa / min. Remove the mold and perform demolding to obtain a green zirconia body.

[0106] II. Sintering:

[0107] 1) Debinding treatment:

[0108] Before sintering, it is necessary to perform debinding treatment on the green zirconia body to remove organic substances and impurities in the green body, such as binders, etc. The debinding treatment is usually carried out at a temperature of 400°C - 700°C for a certain period of time. The holding time depends on the size and shape of the green body and is generally 2 - 4 hours.

[0109] 2) Heating stage:

[0110] After debinding is completed, heat up the debound green body. The heating rate should not be too fast to avoid cracks or deformation of the green body due to thermal stress. Generally, multi-stage heating is adopted. For example, first heat up at a rate of 50 - 100°C / h to 700°C - 1200°C and hold for 1 - 2 hours, and then heat up at a rate of 100 - 200°C / h to the sintering temperature.

[0111] 3) Sintering stage:

[0112] The sintering temperature is usually between 1200°C and 1650°C, and the holding time is 2 - 6 hours. In this stage, particle matter migration occurs in the green body, pores are removed, and the green body gradually densifies.

[0113] 4) Cooling stage:

[0114] After sintering is completed, enter the cooling stage. The cooling rate is to cool down to below 450°C ± 100°C at a rate of 100°C ± 20°C / h, and then naturally cool to room temperature to obtain the implant blank.

[0115] Mechanical and various index tests were conducted on the implant embryos made by using the forming process of the present invention, and the results are shown in the following table. It can be seen from the data that the implant embryos made by using the forming process of the present invention have significantly improved in various indexes.

[0116] As shown in Table 3, static pressing and sintering were carried out according to the above steps to obtain the implant blanks.

[0117] Table 3 Forming conditions of zirconia powder in different embodiments

[0118]

[0119] Table 4 Various indexes of the implant embryos prepared in Example 4

[0120]

[0121] Example 7 Machining and surface treatment

[0122] The implant embryos obtained in Examples 3-6 were machined to obtain the structure in Example 1. The machining was carried out by dividing the tool into processes. Among them, rough machining was carried out using a common alloy end mill, and the tool was selected with a diameter of 5-10 mm. Fine machining was carried out using a special alloy end mill with a selected diameter of 1-10 mm.

[0123] Surface treatment process

[0124] Sandblasting and acid etching of ceramic implants is a surface treatment technology used to improve the bonding ability between implants and surrounding bone.

[0125] Sandblasting treatment is to impact particulate matter with a certain diameter onto the surface of the semi-finished implant at high speed to form a certain roughness. This rough surface can increase the surface area of the implant, provide more space for new bone formation, and is conducive to the generation of bone bonding. At the same time, appropriate roughness is conducive to the adhesion, proliferation, division, differentiation, secretion of extracellular matrix and osteogenesis of osteoblasts.

[0126] Acid etching treatment is to expose the implant to a certain concentration of acid solution for chemical reaction. Microscopic holes will be formed on the surface of the semi-finished implant, and these holes can promote the attachment of the pseudopods of osteoblasts and are conducive to the growth of bone cells.

[0127] In the present invention, the machined implant semi-finished products are first sandblasted and then acid-etched. Uniform primary and secondary holes can be formed on the surface of the product after sandblasting and acid etching. The primary holes are 20-100 um, and the secondary holes are 1-10 um. The formed primary and secondary holes are for osteoblasts to grow in the holes, greatly improving the stability of the product.

[0128] Specifically, the machined implant semi-finished product is first subjected to sandblasting, which includes spraying sand balls onto the surface of the implant semi-finished product. The sand balls are selected from boron carbide, zirconia or alumina, preferably zirconia, and more preferably alumina. Preferably, the diameter of the sand balls is 50-500 μm, preferably 80-400 μm, and more preferably 100-200 μm. Further, the pressure of the sandblasting is 1-10 bar, for example 2-5 bar; the working distance of the sandblasting is 10-50 mm, for example 15 mm, preferably 8-10 mm; the moving speed of the sandblasting is 1-20 mm / s, for example 5 mm / s.

[0129] The etching treatment includes: treating the surface of the sandblasted implant semi-finished product with an etching solution.

[0130] The etching solution includes a first acid and hydrofluoric acid. The first acid can be selected from at least one, two or more of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, etc. Further, the hydrofluoric acid is selected from 30-50 vol% hydrofluoric acid; the first acid is selected from 50-80 vol% nitric acid or 30-50 vol% sulfuric acid, 40-60 vol% phosphoric acid. More preferably, the etching solution is obtained by mixing 30-50 vol% hydrofluoric acid and 50-80 vol% nitric acid, preferably by mixing 35-45 vol% hydrofluoric acid and 60-70 vol% nitric acid. Exemplarily, the etching solution includes hydrofluoric acid (40 vol%) and nitric acid (50 vol%), and the volume ratio of the two is 4:6.

[0131] In the etching solution, the volume ratio of the hydrofluoric acid to the first acid is (2-8):(8-2), preferably (4-6):(6-4), and more preferably 4:6.

[0132] The etching time is 1 min - 120 min, preferably 20-40 min, and more preferably 30 min.

[0133] The etching temperature is 30-100 °C, for example 70 °C, 80 °C.

[0134] Table 5 Sandblasting and acid etching conditions for different green bodies

[0135]

[0136] The implant prepared in Example 11 was compared with a commercially available product (from bredent medical, named Zirconia implant, trade name wSKYT3508, batch number 510132) to prove that the osteocyte growth effect of the product prepared by the present invention (experimental group) is better than that of the commercially available product (control group). See Tables 6.1 and 6.2 for the Micro-CT test data of the animal experiments of the experimental group and the control group, and Table 7 for the hard tissue section test data of the animal experiments of the experimental group and the control group. From Tables 6.1, 6.2, and 7, Figure 14 , Figure 15 , Figure 16 , Figure 17 , Figure 18 it can be seen that for the ceramic implant prepared by the present invention through the sandblasting and acid etching process, hard bone is evenly distributed on the surface of the product, and the bone growth area is larger than that of the competing product, proving that the sandblasting and acid etching process prepared by the present invention is superior to the surface treatment processes existing in the market.

[0137] Materials for animal experiments:

[0138] 1. Experimental animals: A number of healthy adult beagle dogs, with a body weight of 15 - 20 kg, half male and half female, without oral diseases and systemic diseases.

[0139] 2. Ceramic implants: Ceramic implants customized according to the alveolar bone size of beagle dogs (prepared according to the method of Example 11), with the surface treated by sandblasting and acid etching to facilitate bone bonding.

[0140] 3. Surgical instruments: Conventional oral implant surgical instruments, including implant machines, dental drills, screwdrivers, etc., all of which have been strictly disinfected.

[0141] 4. Imaging equipment: Micro-CT and X-ray machines for imaging examinations at different time points before, during, and after implantation.

[0142] 5. Histological detection reagents: Fixative, decalcifying solution, embedding agent, hematoxylin-eosin (HE) staining reagent, etc.

[0143] Animal experiment method

[0144] 1. Grouping:

[0145] The beagle dogs were randomly divided into an experimental group and a control group, and the number of each group was determined according to statistical calculations, generally not less than 5 in each group. Ceramic implants were implanted in both the experimental group and the control group.

[0146] 2. Preoperative preparation:

[0147] The beagle dogs were fasted for 12 hours and water-deprived for 6 hours before surgery.

[0148] General anesthesia was induced by intravenous injection of sodium pentobarbital.

[0149] Oral cavity cleaning and disinfection: wipe the oral mucosa and gums with iodophor cotton balls.

[0150] 3. Implant surgery:

[0151] Under aseptic conditions, incise the mucosa at the top of the alveolar ridge of beagle dogs, and flap to expose the alveolar bone.

[0152] According to the implant specifications, use an implant drill to prepare the implant socket, pay attention to controlling the rotation speed and temperature to avoid bone burns.

[0153] Implant the experimental or control group into the implant socket, install the protective cap, and suture the wound.

[0154] 4. Postoperative care:

[0155] Administer antibiotics after surgery to prevent infection, and inject continuously for 3 - 5 days.

[0156] Feed the animals with liquid food for 1 week after surgery, and then gradually transition to a normal diet.

[0157] Regularly observe the wound healing situation, and record any complications such as swelling, bleeding, and infection.

[0158] 5. Observation indicators

[0159] 5.1 Clinical observation:

[0160] Inspection time: every day after surgery

[0161] Inspection content: During the postoperative observation period, observe and record the general observation indicators of the experimental animals every day, including appearance signs, mental state, behavioral activities, local irritation, fecal characteristics, food consumption, etc.; at the same time, observe whether there are abnormal bleeding and other symptoms in the postoperative wound. In case of local symptoms or abnormal death of the animals, detailed records should be made.

[0162] 5.2 Micro-CT examination:

[0163] Inspection time: 4 weeks (6 animals), 8 weeks (6 animals), 13 weeks (6 animals), 26 weeks (6 animals) after surgery; one animal from each of the experimental and control groups is selected for each inspection.

[0164] Inspection content: Detect the implant and the attached bone tissue through Micro-CT, including: trabecular bone thickness, trabecular bone number, trabecular bone spacing, bone volume of the sampled tissue, and tissue volume of the sampled tissue. Measure the TB.Th, TB.N, Tb.Sp, BV, TV, and BV / TV% values of the experimental group and the control group. The results are expressed as mean ± standard deviation, and group comparison is used. The P value is calculated by the T test. A P value < 0.05 is considered statistically significant.

[0165] 5.3 Histological examination:

[0166] Inspection time: 4 weeks (6 samples), 8 weeks (6 samples), 13 weeks (6 samples), 26 weeks (6 samples) after surgery; sharing samples with Micro-CT

[0167] Staining method: Methylene blue - Acid fuchsin staining

[0168] Inspection content: Take tissue specimens from the implantation site and its periphery, fix them with 10% neutral formalin, prepare standardized grinding slices, stain with methylene blue - acid fuchsin, measure Im.Pm (implant perimeter), Tb.In.Pm (perimeter of the contact between the implant and the cancellous bone part), CtIn.Pm (perimeter of the contact between the implant and the cortical bone part), and BIC (bone implant contact, implant - bone bonding rate). The results are expressed as mean ± standard deviation. Inter - group comparison is used, and the P - value is calculated by t - test. A P < 0.05 is considered statistically significant.

[0169] 6. Data statistical analysis

[0170] Statistical software is used to analyze the experimental data. Measurement data are expressed as mean ± standard deviation (x ± s). Inter - group comparison is performed using t - test or analysis of variance. A P < 0.05 is considered statistically significant.

[0171] 7. Results

[0172] 7.1 Clinical observation:

[0173] All experimental animals survived normally, with no abnormalities in postoperative behavior or food intake. The wound did not show redness, swelling, purulent discharge, or sinus tract formation. No abnormal neurological symptoms occurred during or after the operation, and there was no gait instability or aggressive behavior during the observation period; the body weights of the experimental animals increased normally at 4 weeks, 8 weeks, 13 weeks, and 26 weeks after surgery (see Figure 13 ), that is, the animals did not have eating disorders caused by the surgical operation.

[0174] 7.2 Micro - CT inspection:

[0175] Table 6.1 Micro - CT inspection results table (X ± S)

[0176]

[0177] Note: n = 3; *P < 0.05.

[0178] Table 6.2 Micro - CT inspection results table (X ± S)

[0179]

[0180]

[0181] Note: n = 3; *P < 0.05.

[0182] In this study, micro-computed tomography (Micro-CT) and related analysis software were used to accurately calculate BV / TV, Tb.Th, Tb.N, Tb.Sp, and total bone volume within the region of interest, in order to analyze bone regeneration and reconstruction during different bone healing periods.

[0183] BV / TV: trabecular bone volume / total bone tissue volume, which can directly reflect changes in bone mass;

[0184] Tb.Th: average thickness of trabecular bone. When osteoporosis occurs, the value of Tb.Th decreases;

[0185] Tb.N: trabecular bone number, which is the number of intersections between bone tissue and non-bone tissue within a given length. When osteoporosis occurs, this value decreases;

[0186] Tb.Sp: average trabecular separation, which is the average width of the medullary cavity between trabecular bones. When osteoporosis occurs, the value of Tb.Sp increases;

[0187] Total bone volume: within the region of interest, it is defined as the volume of bone tissue

[0188] From Tables 6.1, 6.2, Figure 14 and Figure 15 it can be seen that at 4 weeks, 8 weeks, 13 weeks, and 26 weeks after surgery, there were no significant differences in bone regeneration and reconstruction between the test group and the control group implants in terms of BV / TV, Tb.Th, Tb.N, TbSp, and total bone volume around the implants; as the cycle extended, the bone mass around the implants showed an obvious upward trend.

[0189] 7.3 Histological examination:

[0190] Based on qualified staining, quantitative analysis was performed on slides stained with methylene blue and acid fuchsin respectively.

[0191] 1. Place it under the microscope and open the OsteoMeasure analysis software. The OsteoMeasure bone measurement software is developed by OsteoMetrics, Inc. It is currently the most technically mature and professional bone measurement software in the world. Its measurement results are highly authoritative and widely recognized internationally. It is a system that can intelligently and quickly measure and calculate bone sample parameters, and is a dedicated system for the International Chinese Bone Research Society to study bone tissue morphology. This system uses a high-pixel CCD, combined with an advanced motorized microscope stage, and advanced software enables researchers to automatically or manually measure and analyze bone samples, and can complete all indicators in clinical indicators and basic applied research in hospitals. Nowadays, as a professional software method for measuring bone tissue and bone morphology, it is widely used in basic medical research and clinical diagnosis fields. Its authority is widely recognized internationally and has been recommended by the International Chinese Bone Research Society.

[0192] 2. Set the parameters for bone-bonding morphometric analysis, including three parameter names: Implant (implant), Ct Interface (cortical bone contact surface), and Tb Interface (cancellous bone contact surface), and Ct Bone (cortical bone).

[0193] 3. Select the analysis area with the implant and analyze it under a 4x microscope. Mark the cancellous bone with Bone, the cortical bone with Ct Bone (both the cortical bone and cancellous bone are the areas seen within the implant field of view), the cancellous bone contact surface with Tb.In.Pm, the cortical bone contact surface with Ct.In.Pm, and the implant perimeter with Im.Pm.

[0194] 4. Export the relevant parameter values and the analysis area diagram from the bone tissue morphology analysis measurement system. Organize the data and add units to form the final data table.

[0195] 5. The blue area represents cancellous bone, the removed part in the blank area above the cancellous bone, the middle red area outside the pink line, the pink solid area represents cortical bone, the light yellow line represents the contact surface between the implant and cancellous bone, and the dark blue line represents the contact surface between the implant and cortical bone.

[0196] 6. Result calculation: (Perimeter of cancellous bone contact surface + Perimeter of cortical bone contact surface) / Implant perimeter = BIC (%) (bonding degree)

[0197] The results are shown in Table 7:

[0198] Implant-bone contact rate (bone implant contact, BIC): Implant-bone contact area / Total available area of the implant.

[0199] Table 7 Results of hard tissue section examination (X ± S)

[0200]

[0201] Note: BIC = (Tb.In.Pm + Ct.In.Pm) / Im.Pm; n = 3; *P < 0.05.

[0202] From the above table, Figure 16 and Figure 18 it can be seen that there was no significant difference in the BIC (%) binding rate between the experimental groups and the control group in each cycle; in the initial stage of implantation (4 weeks after surgery), a small amount of new bone could be seen on the surface of the implant, and at 26 weeks, a large amount of new bone had appeared on the surface of the implant; and from 4 weeks to 26 weeks after surgery, the BIC (%) binding rate was positively correlated with the implantation cycle, indicating that the fusion of the implant and new bone became better with the extension of the cycle; the average value of BIC (%) in the experimental group reached 37.33% at 4 weeks after surgery, 45.00% at 8 weeks after surgery, 60.00% at 13 weeks after surgery, and 65.67% at 26 weeks after surgery.

[0203] 8 Conclusions

[0204] The ceramic dental implant (model: batch number: C2312004) produced by the experimental group, Beijing Ruici Medical Technology Co., Ltd. has high safety and good effectiveness. In terms of safety, there was no obvious difference between the clinical observation of the ceramic dental implant system and the control group; in terms of effectiveness, the ceramic dental implant system showed no significant difference from the control product in terms of Micro-CT and bone bonding rate, and showed good bone bonding effect.

[0205] Since the implant product prepared by the present invention is a Class III medical device implant, there are strict requirements for the fine washing and packaging environment of the product and the initial contaminating bacteria and particles of the product after fine washing and packaging. The fine washing and packaging environment of the product should not be lower than 100,000 class, and the product after fine washing and packaging should meet the requirement that the initial contaminating bacteria should be ≤100 cfu / g, the washing parameters are temperature 40 - 80°C, and the washing time is 20 - 60 minutes.

[0206] There are 3 types of medical device sterilization methods, radiation sterilization, ethylene oxide sterilization, and high-pressure steam sterilization. The color of the ceramic material will change after radiation sterilization, and its mechanical properties will also decline, so it is not adopted. The operation of high-pressure steam sterilization is complex and will also affect the timeliness of the material, so it is not adopted either. Ethylene oxide sterilization will not affect the product performance, and batch operation is more convenient, so ethylene oxide sterilization is adopted. After the product is sterilized and returned to the factory, tests need to be carried out, including product sterility, bacterial endotoxin ≤0.25 EU / mL, and ethylene oxide residue ≤10 μg / g.

[0207] The specific embodiments of the present invention have been exemplarily described above through examples. However, the protection scope of the present invention is not limited to the above exemplary embodiments. Any modifications, equivalent substitutions, improvements, etc. made by those skilled in the art within the spirit and principle of the present invention shall be included within the protection scope of the claims of the present invention.

Claims

1. An integrated high-strength implant, characterized in that: The implant comprises an implant and a base, wherein the base is arranged at the end of the implant and is integrally formed with the implant. The surface of the implant has uniform primary and secondary holes, wherein the primary holes have a diameter of 20-100um and the secondary holes have a diameter of 1-10um.

2. The integrated high-strength implant according to claim 1, characterized in that: A square groove is arranged in the base, and the square groove is used for connecting the crown. Preferably, the outer wall of the base is provided with a connecting groove, and the connecting groove is used to cooperate with an external carrying body, for example, the external carrying body can be inserted into the groove.

3. The integrated high-strength implant according to claim 1 or 2, characterized in that: The implant comprises a soft tissue connection area and a threaded area. The soft tissue connection area is located at the upper part of the implant. When the implant is implanted, the soft tissue connection area corresponds to the soft tissue and has an arc-shaped structure. Preferably, a cutting edge is provided at the lower portion of the threaded zone, and the cutting edge is eccentric by 0.1-0.5 mm, preferably the cutting edge is eccentric by 0.1-0.3 mm. Preferably, the threaded area includes a base, the threads protrude radially outward from the surface of the base, the diameter of the threaded area gradually decreases from top to bottom, and the bottom diameter of the threaded area is 0.1-0.5 mm smaller than the top diameter. Preferably, the thread of the threaded zone is a multi-thread, such as a double-thread or triple-thread. Preferably, the thread surface is a smooth structure.

4. A method for forming the integrated high-strength implant according to any one of claims 1 to 3, characterized in that: The method comprises the following steps: S1. The ceramic powder is loaded into a mold, sealed and cold isostatically pressed to obtain a green body; S2. The green body is degreased and sintered to obtain a green body; S3. Machining the blank to obtain a semi-finished implant; S4. Sandblast and acid-etch the semi-finished implant to obtain the implant.

5. The molding method according to claim 4, characterized in that: The implant powder is selected from at least one of alumina powder, zirconia powder, zirconia toughened alumina powder or alumina toughened zirconia powder, for example, zirconia powder. Preferably, the particle size of the zirconium oxide powder is 1 to 100 nm. Preferably, the cold isostatic pressing comprises the following steps: placing a mold filled with ceramic powder into a high-pressure chamber of a cold isostatic press, starting the machine, gradually applying pressure to 250±50 MPa, maintaining the pressure for 5-10 minutes, and compacting the powder under uniform pressure.

6. The molding method according to claim 4, characterized in that: The steps between step S1 and step S2 include the following steps: depressurizing the high-pressure cavity at a rate of 15±5 MPa / min, demolding, and obtaining a green body. Preferably, the degreasing comprises the following steps: keeping the green body at a temperature of 400° C.-700° C. for 2-4 hours. According to an embodiment of the present invention, the sintering comprises the following steps: firstly degreasing the green body, and then keeping the temperature at 1200° C.-1650° C. for 2-6 hours. Preferably, the debinding comprises the following steps: heating the green body to 700°C-1200°C at a rate of 50-100°C / h, keeping the temperature for 1-2 hours, and then heating to the sintering temperature at a rate of 100-200°C / h.

7. The molding method according to any one of claims 4 to 6, characterized in that: The steps between step S2 and step S3 include the following steps: cooling the sintered green body to below 450°C±100°C at 100°C±20°C / h, and then naturally cooling to room temperature to obtain an implant body.

8. The molding method according to any one of claims 4 to 6, characterized in that: The machined implant semi-finished product is firstly subjected to sandblasting treatment. Preferably, the sandblasting process comprises spraying sand balls onto the surface of the implant semi-finished product, the sand balls are selected from boron carbide, zirconium oxide or aluminum oxide, and the diameter of the sand balls is 50-500 μm. Preferably, the pressure of the sandblasting is 1-10 bar, the working distance of the sandblasting is 10-50 mm, and the moving speed of the sandblasting is 1-20 mm / s.

9. The molding method according to claim 8, characterized in that: The etching treatment includes: using an etching liquid to treat the surface of the implant semi-finished product after sandblasting, so as to form a hole structure on the outer surface thereof. Preferably, the etching solution comprises a first acid and hydrofluoric acid, and the first acid is selected from at least one, two or more of hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and the like.

10. The molding method according to claim 9, characterized in that: In the etching solution, the volume ratio of the hydrofluoric acid to the first acid is (2-8): (8-2). Preferably, the etching time is 1 min-120 min, and the etching temperature is 30-100°C.

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